Circular RNAs and Their Emerging Roles in Immune Regulation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Jan 9

PMID 30619334

Citations 49

Authors

Lan Yang

Jinrong Fu

Yufeng Zhou

Affiliations

Soon will be listed here.

Abstract

Circular ribonucleic acid (RNA) molecules (circRNAs) are covalently closed loop RNA molecules with no 5' end caps or 3' poly (A) tails, which are generated by back-splicing. Originally, circRNAs were considered to be byproducts of aberrant splicing. However, in recent years, development of high-throughput sequencing has led to gradual recognition of functional circRNAs, and increasing numbers of studies have elucidated their roles in cancer, neurologic diseases, and cardiovascular disorders. Nevertheless, studies of the functions of circRNAs in the immune system are relatively scarce. In this review, we detail relevant research on the biogenesis and classification of circRNAs, describe their functional mechanisms and approaches to their investigation, and summarize recent studies of circRNA function in the immune system.

Citing Articles

Circular RNA Formation and Degradation Are Not Directed by Universal Pathways.

Srinivasan A, Mroczko-Mlotek E, Wojciechowska M Int J Mol Sci. 2025; 26(2).

PMID: 39859439 PMC: 11766002. DOI: 10.3390/ijms26020726.

Noncoding RNAs in rheumatoid arthritis: modulators of the NF-κB signaling pathway and therapeutic implications.

Seyedi D, Espandar N, Hojatizadeh M, Mohammadi Y, Sadri F, Rezaei Z Front Immunol. 2024; 15:1486476.

PMID: 39530095 PMC: 11550995. DOI: 10.3389/fimmu.2024.1486476.

Potential role of lncRNA LOXL1-AS1 in human cancer development: a narrative review.

Tang M, Rong Y, Liu S, Wu Z, Ma G, Li X Transl Cancer Res. 2024; 13(4):1997-2011.

PMID: 38737681 PMC: 11082674. DOI: 10.21037/tcr-23-1450.

Epigenetic modulation of long noncoding RNA H19 in oral squamous cell carcinoma-A narrative review.

Rajendran P, Sekar R, Abdallah B, Jh S, Ali E, Jayaraman S Noncoding RNA Res. 2024; 9(2):602-611.

PMID: 38532798 PMC: 10963247. DOI: 10.1016/j.ncrna.2024.01.020.

Circular RNAs and the regulation of gene expression in diabetic nephropathy (Review).

Benitez M, Navarro Y, Azuara-Liceaga E, Cruz A, Flores J, Lopez-Canovas L Int J Mol Med. 2024; 53(5).

PMID: 38516776 PMC: 10998718. DOI: 10.3892/ijmm.2024.5368.

References

Zhou C, Molinie B, Daneshvar K, Pondick J, Wang J, Van Wittenberghe N . Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs. Cell Rep. 2017; 20(9):2262-2276. PMC: 5705222. DOI: 10.1016/j.celrep.2017.08.027. View

Nair V, Zavolan M . Virus-encoded microRNAs: novel regulators of gene expression. Trends Microbiol. 2006; 14(4):169-75. DOI: 10.1016/j.tim.2006.02.007. View

Hansen T, Jensen T, Clausen B, Bramsen J, Finsen B, Damgaard C . Natural RNA circles function as efficient microRNA sponges. Nature. 2013; 495(7441):384-8. DOI: 10.1038/nature11993. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Hubbard A, Rothlein R . Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic Biol Med. 2000; 28(9):1379-86. DOI: 10.1016/s0891-5849(00)00223-9. View

Ivanov A, Memczak S, Wyler E, Torti F, Porath H, Orejuela M . Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015; 10(2):170-7. DOI: 10.1016/j.celrep.2014.12.019. View

Tan S, Gou Q, Pu W, Guo C, Yang Y, Wu K . Circular RNA F-circEA produced from EML4-ALK fusion gene as a novel liquid biopsy biomarker for non-small cell lung cancer. Cell Res. 2018; 28(6):693-695. PMC: 5993747. DOI: 10.1038/s41422-018-0033-7. View

Jansson M, Lund A . MicroRNA and cancer. Mol Oncol. 2012; 6(6):590-610. PMC: 5528350. DOI: 10.1016/j.molonc.2012.09.006. View

Dengler V, Galbraith M, Espinosa J . Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol. 2013; 49(1):1-15. PMC: 4342852. DOI: 10.3109/10409238.2013.838205. View

10.

Ashwal-Fluss R, Meyer M, Pamudurti N, Ivanov A, Bartok O, Hanan M . circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014; 56(1):55-66. DOI: 10.1016/j.molcel.2014.08.019. View

11.

Li Z, Huang C, Bao C, Chen L, Lin M, Wang X . Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015; 22(3):256-64. DOI: 10.1038/nsmb.2959. View

12.

Dunn W, Trang P, Zhong Q, Yang E, Van Belle C, Liu F . Human cytomegalovirus expresses novel microRNAs during productive viral infection. Cell Microbiol. 2005; 7(11):1684-95. DOI: 10.1111/j.1462-5822.2005.00598.x. View

13.

Weng Q, Chen M, Li M, Zheng Y, Shao G, Fan W . Global microarray profiling identified as a potential immune-associated prognosis biomarker for hepatocellular carcinoma. J Med Genet. 2018; 56(1):32-38. DOI: 10.1136/jmedgenet-2018-105440. View

14.

Chen C, Sarnow P . Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science. 1995; 268(5209):415-7. DOI: 10.1126/science.7536344. View

15.

Seidell J . Obesity, insulin resistance and diabetes--a worldwide epidemic. Br J Nutr. 2000; 83 Suppl 1:S5-8. DOI: 10.1017/s000711450000088x. View

16.

Ng W, Marinov G, Liau E, Lam Y, Lim Y, Ea C . Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway. RNA Biol. 2016; 13(9):861-71. PMC: 5014010. DOI: 10.1080/15476286.2016.1207036. View

17.

Liang D, Wilusz J . Short intronic repeat sequences facilitate circular RNA production. Genes Dev. 2014; 28(20):2233-47. PMC: 4201285. DOI: 10.1101/gad.251926.114. View

18.

Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O . Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017; 66(1):22-37.e9. PMC: 5387670. DOI: 10.1016/j.molcel.2017.02.017. View

19.

Pfeffer S, Zavolan M, Grasser F, Chien M, Russo J, Ju J . Identification of virus-encoded microRNAs. Science. 2004; 304(5671):734-6. DOI: 10.1126/science.1096781. View

20.

Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P . Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell. 1993; 73(5):1019-30. DOI: 10.1016/0092-8674(93)90279-y. View